The invention relates to polymerizable macromonomers and dental and medical compositions containing polymerizable macromonomers. The invention provides macromonomers for dental compositions and a process for preparing them. Dental/medical compositions which include macromonomers of the invention have a high adhesion to hard dental tissue and low volumetric shrinkage.
It is an object of the invention to provide an esterified macromonomer within the scope of the general formula: 
wherein Z is an organic moiety, R1 is hydrogen or a substituted or unsubstituted alkyl having from 1 to 12 carbon atoms, oxyalkyl having from 1 to 12 carbon atoms, alkenyl having from 2 to 12 carbon atoms, cycloalkyl having from 5 to 12 carbon atoms, aryl having from 6 to 12 carbon atoms or aralkyl having from 7 to 12 carbon atoms. Each E independently is a hydroxyl group, an organic ester moiety or an inorganic ester moiety and at least one E is a ester containing moiety. n and m each independently is an integer from 2 to 12.
It is the object of the invention to provide an esterified macromonomer obtainable by esterification of at least a portion of the xe2x80x94OH groups of a macromonomer having at least one terminal double bond with at least one derivative of an inorganic or organic acid which introduces pendant groups exhibiting at least one acid moiety selected from the group of consisting of xe2x80x94COOH, xe2x80x94PO3H2, xe2x80x94SO3H, xe2x80x94BO2H and salts thereof. The number of the acid moieties is chosen such that a polymer obtained by polymerizing said monomers has an adhesive strength to dentine of at least 2 MPa.
Prior Art dental/medical compositions such as cements are either water-based ionic cements or resin based materials. The water-based cements have the advantage of a modest adhesion to hard tooth tissues and of a high fluoride ion release from inorganic filler material. They have the disadvantage of high water solubility, low abrasion resistance and an excessive opacity. The resin-based materials have the advantage of excellent mechanical properties, a suitable opacity and low water solubility. They have the disadvantage of a lack of adhesion, a very poor release of fluoride ions from an inorganic filler and a high volumetric shrinkage.
Engelbrecht et al in U.S. Pat. No. 4,806,381 discloses Polymerizable Compounds Containing Acid and Acid Derivatives, Mixtures Containing the Same, and Use Thereof. Blackwell et al in U.S. Pat. No. 4,816,495 discloses Biologically Compatible Adhesive Visible Light Curable Compositions.
These disadvantages of prior art dental compounds and compositions are overcome by the novel and nonobvious compounds and compositions of the invention.
An esterified macromonomer within the scope of the general formula (I): 
wherein Z is an organic moiety. R1 is hydrogen or a substituted or unsubstituted alkyl having from 1 to 12 carbon atoms, oxyalkyl having from 1 to 12 carbon atoms, alkenyl having from 2 to 12 carbon atoms, cycloalkyl having from 5 to 12 carbon atoms, aryl having from 6 to 12 carbon atoms or aralkyl having from 7 to 12 carbon atoms. Each E independently is a hydroxyl group, an organic ester moiety, or an inorganic ester moiety. At least one E is an ester moiety. n and m each independently is an integer from 2 to 12. The esterified macromonomer is obtainable by esterification of at least a portion of the xe2x80x94OH groups of a macromonomer having at least one terminal double bond with at least one derivative of an inorganic or organic acid which introduces pendant groups exhibiting at least one acid moiety selected from the group of consisting of xe2x80x94COOH, xe2x80x94PO3H2, xe2x80x94SO3H, xe2x80x94BO2H or salts thereof. The number of the acid moieties is chosen such that a polymer obtained by polymerizing those monomers has an adhesive strength to dentine of at least 2 MPa.
The invention provides macromonomers esterfied, with organic acids or inorganic acids or derivatives thereof. The esterified macromonomers are useful in composition with or without water, such as water free self-adhesive dental/medical composite. The dental/medical composite comprises a modified macromonomer, and/or di- or poly(methacrylates) containing phosphoric acid ester groups or salts thereof, polymerizable monomers, acid-reactive and/or reactive and/or non-reactive fillers, diluents, polymerization initiators and stabilizers. Composition in accordance with the invention include polymerization initiators, such as thermal initiators, redox initiators and/or photoinitiators. The new adhesive dental composite develops adhesion to dentine of about 4 MPa. Fillers of high X-ray absorbence provide radio-opacity values greater than that of the same thickness of aluminium.
Preparation of Epoxide-macromonomers
Macromonomers in accordance with the invention are produced by chemical modification of macromonomers containing hydroxyl groups. Macromonomer containing hydroxyl groups useful for making esterified macromonomer in accordance with the invention are described for example in Polym. Bull. 27 (1992) 511-517, Acta Polym. 42 (1991) 17-20 and DE 4217761.8 incorporated herein by reference. Preferred polymerizable compounds for use in compositions in accordance with the invention are within the scope of general formulas M1-M12 as follows: 
wherein
each E independently is a hydroxyl group, an organic ester moiety or an inorganic ester moiety,
at least one E is an ester moiety,
R is a diether or a diester containing moiety or tertiary amine,
R1 is hydrogen or a substituted or unsubstituted alkyl having from 1 to 12 carbon atoms, oxyalkyl having from 1 to 12 carbon atoms, alkenyl having from 2 to 12 carbon atoms, cycloalkyl having from 5 to 12 carbon atoms, aryl having from 6 to 12 carbon atoms or aralkyl having from 7 to 12 carbon atoms,
R2 is a difunctional substituted or unsubstituted alkyl group having from 1 to 12 carbon atoms, alkenyl group having from 2 to 12 carbon atoms, cycloalkyl having from 5 to 12 carbon atoms, aryl having from 6 to 12 carbon atoms or aralkyl having from 7 to 12 carbon atoms,
R3 is hydrogen or a substituted or unsubstituted alkyl group having from 1 to 12 carbon atoms, alkenyl group having from 2 to 12 carbon atoms, cycloalkyl having from 5 to 12 carbon atoms, aryl having from 6 to 12 carbon atoms or aralkyl having from 7 to 12 carbon atoms,
R4 is a substituted or unsubstituted aryl having from 6 to 12 carbon atoms,
and n is an integer of at least 1.
Preferably R is a moiety within the scope of the general formulas: 
(according to R of the foreclosures)
wherein X is C(CH3)2, xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94COxe2x80x94, or xe2x80x94SO2xe2x80x94.
Preferably R4 is a moiety within the scope of the general formulas: 
wherein X is C(CH3)2, xe2x80x94CH2xe2x80x94, xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94COxe2x80x94, xe2x80x94SO2xe2x80x94.
Preferably E is a hydroxyl group, an ester moiety, a boric acid moiety, a sulfuric acid moiety or a phosphoric acid moiety.
Macromonomers within the scope of general formula M-1 are synthesized in two steps. At first an oligomer mixture is obtained by reaction of an xcex1,xcex2-unsaturated acids with excessive amounts of a diepoxide, such as bisphenol-A diglycidyl ether (DGEBA), bisphenol-F diglycidyl ether (DGEBF), butanediol diglycidyl ether (BDODGE), tetrahydro terephtalic acid diglycidyl ether or diglycidyl aniline. This mixture contains the bis-ester of the diepoxide along with the mono-ester and unreacted diepoxide as governed by the ratio of the diepoxide and the unsaturated acid. The formation of macromonomers follows in a second reaction of the previous reacted oligomers with dicarboxylic acids to M-1 (DE 4217761.8). 
Instead of dicarboxylic acids in the second step also primary monoamines were used which react to macromonomers M-2, disecondary diamines which react to macromonomers M-3, (J. Klee et. al. Polym. Bull. 27 (1992) 511-517, DD 279667) and bisphenols which react to macromonomers M-6.
During the epoxide ring cleavage by carboxylic acids an amount equal to approximately 20 percent by weight of the epoxide groups is opened to the corresponding primary alcohols: 
Consequently, macromonomers M-1, M-2, M-3 and M-6 wherein each E is hydrogen contain both types of molecules having primary and/or secondary alcohol units.
The resulting macromonomers are viscous liquids or solids which are soluble in THF, CHCl3 and DMF. Their glass transition temperatures are relatively low (between 0 and 50xc2x0 C.) depending on the nature of the comonomer and the molecular mass of the macromonomers.
The degree of polymerisation Pn and the macromonomer value n depends on the mol ratio of the monomers, the diepoxide and the comonomers and were calculated by             P      n        =                                        1            +            r                                1            -            r                          ⁢                  xe2x80x83                ⁢        and        ⁢                  xe2x80x83                ⁢        n            =              r                  1          -          r                      ,
respectively using r=z/x. That means each macromonomer M is a definite mixture of a series of homologous oligomers (n=1,2,3,4,5, . . . ) and contains a certain amount of the molecule (n=0).
Macromonomers M-5 wherein each E is hydrogen are prepared by one-step reaction of the diepoxides, disecondary diamines and 2,3-epoxypropyl-(meth)acrylate according to the following equation: 
A second route to obtain macromonomers M-5 wherein each E is hydrogen is a two-step reaction. In the first step the diepoxide is reacted with the disecondary diamine to an xcex1,xcfx89-terminated prepolymer. In the second step the obtained prepolymer is reacted with 2,3-epoxypropyl-(meth) acrylate (DD 277689, J.Klee, H.-H. Hxc3x6rhold, H.Schxc3xctz, Acta Polym. 42 (1991) 17-20).
Instead of disecondary diamines in the second step also were used primary monoamines react to macromonomers M-4, bisphenols react to macromonomers M-7 or dicarboxylic acids react to macromonomers M-8.
Macromonomers M-9 wherein each E is hydrogen are prepared by reaction of diepoxides, dicarboxylic acids and aminoalkyl (meth)acrylates according to the following equation: 
Instead of dicarboxylic acids, primary monoamines were used to prepare macromonomers M-10, disecondary diamines were used to prepare macromonomers M-11, bis-phenols were used to prepare macromonomers M-12.
Specific macromonomers M-1 to M-12 representing molecules of n=0, n=1 or n=2 may be isolated from the mixture by fractionated precipitation or by chromatography and subjected to esterification as described.
Esterification of Macromonomers
The reaction of epoxide macromonomers M-1 to M-12 with organic acids or inorganic acids or derivatives thereof leads to macromonomers having ester moieties.
As derivatives of organic acids preferably were used succinic acid anhydride, maleic acid anhydride, dichloromaleic acid anhydride, dimethyl maleic acid anhydride, malonic acid anhydride, aconit acid anhydride, adipic acid anhydride, 3,3-tetramethylen glutaric acid anhydride, cyclohexen-1,2 acid anhydride, nadinic acid anhydride, phthalic acid anhydride, trimellitic acid anhydride, 2-sulfo-benzoic acid anhydride, 2-sulfo succinic acid anhydride, phthalic acid anhydride p-(O-phosphat), phthaloyl-chloride, succinic acid dimethyl ester.
As derivatives of inorganic acids preferably were used phosphorous penta chloride, phosphorous trichloride, phosphorous oxychloride, sulfuryl chloride, thionyl chloride, phosphor thionyl chloride, boric acid anhydride, boron trichloride.
It is possible to synthesize the esterified macromonomers without using any catalysts in the cases of M-2 to M-5, M-10, M11 (n greater than 0). These macromonomers contain the catalytic active amine in the backbone of the molecule. The use of catalysts such as tertiary amines or quarterly ammonium salts is possible and in the case of esterification of M-1, M-6, M-7, M-8, M-9 and M-12 necessary.
The esterification of the macromonomer hydroxyl groups is carried out in pure substance or in diluted solutions. Preferably, solvents such as tetrahydro furane, dioxane, or polymerizable monomers such as triethylenglycol bismethacrylate, diethylenglycol bismethacrylate, dioxolan bismethacrylate, vinyl-, vinylen- or vinyliden-, acrylate- or methacrylate substituted spiroorthoesters and 2,2-Bis[p-(acryloxyethoxy)phenyl]propane are present during esterification of the macromonomers. The temperature is in the preferred range of 60xc2x0 C. to 120xc2x0 C.
Dental/medical Application
A dental/medical composite, a dental/medical sealant, a dental/medical adhesive and a dental/medical primer have been developed comprising a modified xcex1,xcfx89-(meth) acryloyl terminated macromonomer notably a di- or poly(meth)acrylate monomer having phosphorous ester groups or salts thereof, polymerizable monomers, fillers, polymerization initiators and stabilizers.
As di- or poly(meth)acrylate monomer having phosphorous ester groups and salts thereof are employed pentaerythrit triacrylate monophosphate, dipentaerythrit pentaacrylate monophosphate, glycerol di(meth)acrylate monophosphate, triethylenglycol (meth)acrylate monophosphate.
As organic polymerizable monomers were used mono- and polyfunctional (meth)acrylates, such as polyalylenoxide di- and poly(meth)acrylates, urethane di- and poly(meth)acrylates, vinyl-, vinylen- or vinyliden-, acrylate- or methacrylate substituted spiroorthoesters, spiroorthocarbonates or bicyloorthoesters. Preferably were used diethylenglycol dimethacrylate, triethylenglycol dimethacrylate, 3,(4),8,(9)-di-methacryloyloxymethyltricyclodecane, dioxolan bismethacrylate, glycerol trimethacrylate, furfuryl methacrylate in a content of 5 to 80 wt-%.
As polymerization initiators are used thermal initiators, redox initiators and/or photo initiators in a content of 0,001 to 3 wt-%.
Thermal initiators are initiators such as peroxides, peresters, perketals, peroxy carbonates, hydroxyperoxides, persulfates and azo compounds preferably dibenzoyl peroxide, cumol hydroperoxide, diisopropyl peroxycarbonate, dipotassium persulfate, azobisisobutylonitril.
Preferred redox initiator systems for use in compositions in accordance with the invention are peroxide/amine systems, such as peracid/amine, perester/amine, perketal/amine, peroxycarbonate/amine and hydroxyperoxide/amine systems; peroxide/metal ion salts, such as ascorbic acid/peroxide/metal ion compounds, (thio)barbituric acid/peroxide/metal ion compounds, metal ion compounds/sulfinates, metal ion compounds/(thio)barbituric acid; transition metal carbonyl compounds and halogenids of organic compounds; boralkyl compounds, peroxysulfates and thiols. Most preferred redox-initiators are benzoylperoxide/N,N-bis-(xcex2-hydroxyethyl)-p-toluidine, benzoylperoxide/N,N-bis-(xcex2-hydroxyethyl)-p-benzoic acid ethylester, benzoylperoxide/tributylamine, cumol hydroperoxide/N, N-bis-(xcex2-hydroxyethyl)-p-toluidine, diisopropyl peroxycarbonate/dimethylbenzylamine.
Preferred photoinitiators for use in polymerizable compositions in accordance with the invention which include macromonomers with the scope of general formulas M-1 through M-12 are camphorquinone, benzophenone and 2,2-dimethylbenzylketal.
Preferred fillers for use in compositions in accordance with the invention include inorganic compounds, such as La2O3, ZrO2, BiPO4, CaWO4, BaWO4, SrF2, Bi2O3, glasses and/or organic fillers, such as polymer granulate. Dental/medical composite compositions of the invention preferably include filler in an amount from about 50 to about 85 percent by weight. Dental/medical adhesive compositions of the invention preferably include filler in an amount from about 50 to about 65 percent by weight. Dental/medical sealant compositions of the invention preferably include filler in an amount from about 10 to about 50 percent by weight.
Dental/medical composite compositions, adhesives and sealant of the invention include one-component and two-component paste/paste and powder/ liquid-material which is to be mixed immediately before use.
Shrinkage of composite compositions of the invention is preferably less than 4.5 and more preferably less than 1.5 percent by volume. Adhesive dental composite compositions of the invention containing radio-opaque fillers preferably provide a radio-opacity of at least 1.5 mm/mm Al, more preferably at least 3 to 7 mm/mm Al, and most preferably at least 7 mm/mmAl.
The self-adhesive dental/medical composites compositions in accordance with a preferred embodiment of the invention have a fluoride release of at least 1 xcexcg/cm2, more preferably at least 1-3 xcexcg/cm2, and most preferably at least 3-10 xcexcg/cm2.
Self-adhesive dental/medical composites compositions in accordance with a preferred embodiment of the invention have an opacity of at least 40%, more preferably at least 20-40%, and most preferably at least 5-20%.
The setting time of the adhesive dental/medical adhesive compositions in accordance with a preferred embodiment of the invention at 37xc2x0 C. is between 1 minute and 60 minutes, more preferably between 5 and 30 minutes and most preferably between 2 and 5 minutes. The setting time of adhesive compositions in accordance with a preferred embodiment of the invention at 23xc2x0 C. is preferably between 10 minutes and 300 minutes more, preferably between 5 and 100 minutes and most preferably between 5 and 20 minutes.
Dental/medical composition in accordance with the invention is characterised by having an adhesion to dentine of at least 2 MPa; a fluoride release of at least 1 xcexcg Fxe2x88x92 per week and per cm2 of the exposed surface of the composition; an opacity of at least C0,7=40%; and a compressive strength of at least 200 Mpa.
In the following examples bond strength to dentin is measured using extracted human teeth. The teeth used for the shear bond strength test are treated in 1% sodium hypochlorite for one hour and then stored in distilled water in a refrigerator at about 4xc2x0 C. until needed. The teeth are washed with water, mechanically sanded with 320 grit carborundum paper until a flat dentin surface is exposed.
The teeth are then individually blown dry with compressed dry air to ensure the dentin surface is free from noticeable moisture. A small plastic straw with 5 mm inner diameter and 2 to 3 mm in length is filled with the polymerizable composition being tested and seated on the dentin so as to form a post without pressure. The upper open end of the straw is covered with a thin film and cured. The specimens are then stored in distilled water at 37xc2x0 C. for 24 hours. The teeth are then vertically mounted in a 7 cm ring using gypsum to provide a base for testing with the post at right angles thereto. The mounted specimens are then loaded in shear in an Zwick device model number 1455 manufactured by Zwick GmbH for measurement of adhesion of the post to dentin at 1 mm/minute crosshead speed. The load is applied parallel to the prepared tooth surface and at right angles to the post until fracture occurred. The shear bond strength is then calculated.
In the examples Fluoride Release is measured by making three 1xc3x9720 mm (diameter) discs of each material. Each disc is placed in 25 ml water stored for a week at 37xc2x0 C. Using an ion selective electrode, the fluoride concentration in mg Fxe2x88x92/cm2 is determined for each disc. The average value of the three discs is recorded.
In the Examples compressive strength is measured according to ISO 9917, EN 29917; flexural strength is measured according to ISO 4049, EN 24049; elastic modulus is measured according to ISO 4049, EN 24049; opacity is measured according to ISO 9912, EN 29912; IR spectra are measured using a Fourier transformation Infra Red spectrometer at 23xc2x0 C.